Immunology Flashcards
Define immunology
The study of the physiological mechanisms that we use to defend our bodies against invasion by other organism
Hypervariable regions
Antibodies have 3 and these determine the complementary fit between the antigen and the antigen binding site of the antibody
CDR’s
Complementary determining regions (part of the antibody and align with the loops at the end of the variable domain) which interact with the antigen and give the antibody specificity
Antigen binding
Bind to the antigen binding site of the antibody by non covalent forces (hydrogen, ionic, VDWs and hydrophobic)=weak bonds so a large number is required to ensure the 2 parts bind together
Antibody affinity
Strength of the total non-covalent interactions with a single antigen binding site on the antibody and a single epitope on the antigen
Antibody avidity
Overall strength of multiple interactions between an antibody with multiple antigen binding sites and a complex antigen with multiple epitopes
Antibody cross-reactivity
Antibody with an antigen binding site complementary to a specific antigen can also recognise different antigens with a similar structure
IgG
- Gamma heavy chain
- Must abundant immunoglobulin
- Found in the blood and extracellular fluid
- Variability of the heavy chain at the hinge region gives rise to 4 different subclasses which have subtly different functions
- Activates the classical complement pathway
- Can be actively transported across the placenta to give the foetus passive immunity and therefore protect it
IgA
- alpha heavy chain
- Variation of the heavy chain at the hinge region gives rise to 2 different subclasses which have subtly different functions
- found in breast milk
- multimeric due to formation of J chains, but IgA in the blood is monomeric
- monomer in the blood and dimer in secretion
- Secretion protects mucosal surfaces
- Secretory component of antibody protects it from degradation
IgM
- mu heavy chain
- first immunoglobulin synthesised from infection in the primary immune response
- 5 monomers joined and held together by J chains=multimeric
- activates agglutination and the complement pathway
- multiple binding sites allow for agglutination and to compensate for the low affinity
- mainly found in the blood
IgE
- epsilon heavy chain
- produced to defend against parasitic infections and allergic reactions
- binds to the high affinity Fc receptors on the mast cells and basophils which are complementary to this specific antibody
- the cross linking by antigen triggers the mast cell activation, degranulation and hence histamine and other inflammatory mediator release
- found at low concentrations/levels within the blood serum
IgD
- sigma heavy chain
- very low blood serum concentration
- Involved in the B cell development and activation
Light chains
Can be either both kappa or both lambda (cannot be one of each because the antibody molecule is symmetrical)
Antibody roles
Roles in medicine, laboratory science and in defence
Laboratory science antibody roles
vast range of diagnostic and research applications
Medicine antibody roles
- Monoclonal antibody therapy for cancer treatment
- Antibody levels can help diagnose disease and monitor disease progress
- Pooled antibodies for passive immunity/therapy
Defence antibody roles
- Neutralisation of toxins by antibodies binding to antigens/toxin molecules
- Passive immunity in newborns with the antibodies gained from the mother
- Opsonisation=coating of the pathogens with antibodies (proteins) to promote phagocytosis, aiding the phagocytes
- Agglutination=antibodies can clump the pathogens together due to their multiple antigen binding sites
- Complement activation via the classical pathway
Where are the B cells produced and mature?
Produced by haematopoietic stem cells in the bone marrow and mature here also before being released into the bloodstream/circulation as naïve B lymphocytes
Role of B lymphocytes
Occur in humoral immunity and if complementary antigen to binding site is encountered, cell proliferation occurs by clonal selection and antibodies of the same specificity will be synthesised
Antigen epitope
The specific part of the antigen to which the receptor binds. Antigens have multiple epitopes so a single antigen can be targeted by multiple antibodies
B cell receptor
Membrane bound antibody which binds to the epitope of antigens. Also consists of a di-sulfate linked heterodimer with an IgA and IgB component
Di-sulfate linked heterodimer
Cytoplasmic tail is long enough to interact with the intracellular components and trigger a cascade
Immunoglobulin gene rearrangement
- Accounts for multiple B cell receptors
- Occurs in bone marrow when progenitor B cells are converted to mature B cells
- Immature B cells begin with germline DNA
- Heavy chain has 3 gene segments=V,D and J regions
- Regions are composed of many segments and a singular segment is selected from each region to join to the constant region
- VDJ regions formed from recombination with addition/removal of DNA, then transcription and splicing
- light chain is V and J=no D
- 3 enzymes involved=kappa, lambda, all heavy
VDJ recombinase
Discards unwanted loops of DNA
-Includes enzymes RAG 1 and RAG 2
Alternative RNA splicing
IgD and IgM are co-expressed
Plasma B cell
produces antibodies
-requires an accessory signal from microbial constituents or activation from a T cell
Memory B cell
prepares for future infections=subsequent infections with the same antigen
Somatic hypermutation and affinity maturation
improves antibody quality
IgM BCRs
only immunoglobulin receptor which can recognise PAMPs
Activation by T helper cells
- Antigen binds to BCR and is internalised by B cell
- degraded into peptides on presented on membrane via MHC class 2 receptors
- dendritic cell also has antigen presented in MHC class 2
- dendritic antigen recognised by CD4 T helper cell
- T cell migrates to lymph nodes and encounters B cell with the same antigen=activates
- B cell proliferates and divides
Ig class switching
- Gene segment rearrangement in the constant region
- Secreted cytokines switches class
Somatic hypermutation and affinity maturation
- more specialised BCR
- once bound to antigen, AID enzyme alters variable region in B cell DNA=introducing point mutations to AT
- Point mutations change the antibody structure helping the antibody bind more strongly to the antigen
- weaker binding antibodies are selected against and don’t survive
- leads to improvement of antibody quality
Primary antibody response
Involves IgM=not very protective
Secondary antibody response
Class switch so memory cells change from IgM to IgG
Cytokines
- secreted by immune cells
- small secreted proteins
Type 1 interferons
Activates natural killers and anti viral defence
Type 2 interferons
Produced by T cells usually and proinflammatory
Pre-infection body defences
Mechanical, chemical and microbiological
Cytokine storm
Overproduction of cytokines leading to accumulation of immune system cells=can lead to death
Defence against bacteria
- Surface defences
- fever
- phagocytosis
- antibody opsonisation
- complement activation via the alternative pathway
- release of inflammatory mediators and acute phase proteins
Defence against viruses
-surface defences
-interferons
-Natural killer cells
-release of inflammatory mediators and acute phase proteins
-T cells mainly resolving infection
antibody, complement, ADCC
Gram positive
Violet, 1 cytoplasmic membrane, staph aureus not e coli (gram negative)
Immune system function
Prevent infections by non self molecules
- too much=immune hyper-activation autoimmunity
- too little=infections
Pathogen recognition
- bacteria enter body
- PRR’s recognise PAMPs
- trigger innate response
- APC’s process and present antigen peptides to adaptive immunity
MHC class 2
- APC’s
- presents exogenous peptides on CD4 helper T cells
MHC class 1
- all nucleated cells
- endogenous peptides on CD8 cytotoxic T cells
MHC
- highly polymorphic
- presents processed antigens to T lymphocytes
MHC class 2
heterodimer of 2 alpha 2 beta
MHC class 1
heterodimer of 3 alpha 1 beta microglobulin
cytotoxic
- direct killing
- membrane perforation
- fas to fasL induced apoptosis
T cell pathway
- precursor in bone marrow
- mature with markers in thymus
- gene rearrangement in cortex and survival of T cells with useful TCR which binds to antigens
- medulla sees elimination of T cells which bind too strongly to MHC
- MHC bound peptide then co-stimulation then cytokine stimulation
Helper
- response modulation
- secrete cytokines
- recruit other immune cells
Cytotoxic T cells
-virally infected or transformed cells
Th1
intracellular infection=macrophage activation
Th2
allergy
Th17
inflammation, bacterial and fungal infection
Treg
- regulation of effector T cell function=regulation of immune response
- switch off naïve or activated effector T cells
- anergy (absence of normal immune response), deletion or regulation
- regulation=T cell not exposed to the antigen or there is insufficient amount of antigen to activate it
Role of Treg
-prevents excessive tissue damage (healthy tissue damage)
Lymphocytes
- regulation by cytokines
- prevent responses against self. central tolerance (thymus) and peripheral tolerance (anergy, deletion, regulation and ignorance) and prevents responses to also avoid tissue damage (lymphocytes apoptose after infection is cleared)
